Coping with aggressive driving : driver accounts of how they manage themselves and others to reduce conflict on the road

Dealing with the aggression of other drivers on the road is an important skill given that driving is a common activity for adults in highly motorised countries. Even though incidents of extreme aggression on the road (such as assault) are reportedly rare, milder forms, some of them dangerous (such as tailgating or deliberately following too closely) are apparently common, and may be increasing. At the very least, this is likely to render the driving environment more stressful, and at worst elevates the risk of crashing by increasing both the level of risky driving behaviours and the likelihood of responses that escalate the situation. Thus the need for drivers to manage incidents of conflict is likely to become increasingly important. However, little research examines how drivers manage their own or others’ aggressive driving behaviour. Recently greater attention has been paid to driver cognitions, especially the attributions that drivers make about other drivers, that then might influence their own driving responses, particularly aggressive or risky ones. The study reported below was the first in a larger exploration of aggressive driving that focussed on driver cognitions, emotions and underlying motivations for aggressive behaviours on the road. Qualitative, in-depth interviews of drivers (n = 30, aged 18-49 years) were subjected to thematic analysis to investigate driver experiences with aggressive driving. Two main themes were identified from these accounts: driver management of self; and driver attempts to influence or manage other drivers. This paper describes the subthemes falling under the management of self main theme. These subthemes were labelled ‘being magnanimous’, ‘chilling out’, ‘slowing down’, and ‘apology/acknowledgment’. ‘Being magnanimous’ referred to situations where the respondent perceived him/herself to be a recipient of another’s aggressive driving and made a deliberate choice not to respond. However, a characteristic of this sub-theme was that this choice was underpinned by the adoption of morally superior stance, or sense of magnanimity. ‘Chilling out’ was a more general response to both the milder aggressive behaviours of other drivers and the general frustrations of driving. ‘Slowing down’ referred to reducing one’s speed in response to the perceived aggressive driving, often tailgating, of another. This subtheme appeared to consist of two separate underlying motivations. One of these was a genuine concern for one’s own safety while the other was more aimed at “getting back” at the other driver. ‘Apology’ referred to how drivers modified their more negative reactions and responses when another driver made gestures that acknowledged their having made a mistake, indicated an apology, or acknowledged the recipient driver. These sub-themes are discussed in relation to their implications for understanding aggressive driving and intervening to reduce it.

The adenine-rich tract in the 5ʹ-end of the hepatitis C virus ORF encodes a peptide regulating the binding of the C protein to RNA

Hepatitis C virus (HCV ) core (C) protein is thought to bind to viral RNA before it undergoes oligomerization leading to RNA encapsidation. Details of these events are so far unknown. The 5ʹ-terminal C protein coding sequence that includes an adenine (A)-rich tract is a part of an internal ribosome entry site(IRES). This nucleotide sequence but not the corresponding protein sequence is needed for proper initiation of translation of viral RNA by an IRES-dependent mechanism. In this study, we examined the importance of this sequence for the ability of the C protein to bind to viral RNA. Serially truncated C proteins with deletions from 10 up to 45 N-terminal amino acids were expressed in Escherichia coli, purified and tested for binding to viral RNA by a gel shift assay. The results showed that truncation of the C protein from its N-terminus by more than 10 amino acids abolished almost completely its expression in E. coli. The latter could be restored by adding a tag to the N-terminus of the protein. The tagged proteins truncated by 15 or more amino acids showed an anomalous migration in SDS-PAGE. Truncation by more than 20 amino acids resulted in a complete loss of ability of tagged C protein to bind to viral RNA. These results provide clues to the early events in the C protein - RNA interactions leading to C protein oligomerization, RNA encapsidation and virion assembly.

Ca2+ regulates the Drosophila Stoned-A and Stoned-B proteins interaction with the C2B domain of Synaptotagmin-1.

The dicistronic Drosophila stoned gene is involved in exocytosis and/or endocytosis of synaptic vesicles. Mutations in either stonedA or stonedB cause a severe disruption of neurotransmission in fruit flies. Previous studies have shown that the coiled-coil domain of the Stoned-A and the µ-homology domain of the Stoned-B protein can interact with the C2B domain of Synaptotagmin-1. However, very little is known about the mechanism of interaction between the Stoned proteins and the C2B domain of Synaptotagmin-1. Here we report that these interactions are increased in the presence of Ca(2+). The Ca(2+)-dependent interaction between the µ-homology domain of Stoned-B and C2B domain of Synaptotagmin-1 is affected by phospholipids. The C-terminal region of the C2B domain, including the tryptophan-containing motif, and the Ca(2+) binding loop region that modulate the Ca(2+)-dependent oligomerization, regulates the binding of the Stoned-A and Stoned-B proteins to the C2B domain. Stoned-B, but not Stoned-A, interacts with the Ca(2+)-binding loop region of C2B domain. The results indicate that Ca(2+)-induced self-association of the C2B domain regulates the binding of both Stoned-A and Stoned-B proteins to Synaptotagmin-1. The Stoned proteins may regulate sustainable neurotransmission in vivo by binding to Ca(2+)-bound Synaptotagmin-1 associated synaptic vesicles.

The utility of serum CA-125 in predicting extra-uterine disease in apparent early stage endometrial cancer

Objectives: To evaluate the clinical value of pre-operative serum CA125 in predicting the presence of extra-uterine disease in patients with apparent early stage endometrial cancer. Methods: Between October 6, 2005 and June 17, 2010, 760 patients were enrolled in an international, multicentre, prospective randomized trial (LACE) comparing laparotomy with laparoscopy in the management of endometrial cancer apparently confined to the uterus. This study is based on data from 657 patients with endometrial adenocarcinoma who had a pre-operative serum CA125 value, and was undertaken to correlate pre-operative serum CA125 with final stage. Results: Using a pre-operative CA-125 cutpoint of 30U/ml was associated with the smallest misclassification error (14.5%) using a multiple cross-validation method. Median pre-operative serum CA-125 was 14U/ml, and using a cutpoint of 30U/ml, 14.9% of patients had elevated CA-125 levels. Of 98 patients with elevated CA-125 level, 36 (36.7%) had evidence of extra-uterine disease. Of the 116 patients (17.7%) with evidence of extra-uterine disease, 31.0% had elevated CA-125 level. In univariate and multivariate logistic regression analysis, only pre-operative CA-125 level was found to be associated with extra-uterine spread of disease. Utilising a cutpoint of 30U/ml achieved a sensitivity, specificity, positive predictive value and negative predictive value of 31.0%, 88.5%, 36.7% and 85.7% respectively. Overall, 326/657 (49.6%) of patients had full surgical staging involving lymph node dissection. When analysis was limited to patients that had undergone full surgical staging, the outcomes remained essentially unchanged. Conclusions: Elevated CA-125 above 30U/ml in patients with apparent early stage disease is associated with a sensitivity of 31.0% and specificity of 88.5% in detecting extra-uterine disease. Pre-operative identification of this risk factor may assist to triage patients to tertiary centres and comprehensive surgical staging.

Human immunodeficiency virus type 1 subtype C Gag virus-like particle boost substantially improves the immune response to a subtype C gag DNA vaccine in mice

Human immunodeficiency virus type 1 (HIV-1) subtype C is the predominant HIV in southern Africa, and is the target of a number of recent vaccine candidates. It has been proposed that a heterologous prime/boost vaccination strategy may result in stronger, broader and more prolonged immune responses. Since HIV-1 Gag Pr55 polyprotein can assemble into virus-like particles (VLPs) which have been shown to induce a strong cellular immune response in animals, we showed that a typical southern African subtype C Pr55 protein expressed in insect cells via recombinant baculovirus could form VLPs. We then used the baculovirus-produced VLPs as a boost to a subtype C HIV-1 gag DNA prime vaccination in mice. This study shows that a low dose of HIV-1 subtype C Gag VLPs can significantly boost the immune response to a single subtype C gag DNA inoculation in mice. These results suggest a possible vaccination regimen for humans. © 2004 SGM.

Chimaeric HIV-1 subtype C Gag molecules with large in-frame C-terminal polypeptide fusions form virus-like particles

HIV-1 Pr55 Gag virus-like particles (VLPs) are strong immunogens with potential as candidate HIV vaccines. VLP immunogenicity can be broadened by making chimaeric Gag molecules: however, VLPs incorporating polypeptides longer than 200 aa fused in frame with Gag have not yet been reported. We constructed a range of gag-derived genes encoding in-frame C-terminal fusions of myristoylation-competent native Pr55Gag and p6-truncated Gag (Pr50Gag) to test the effects of polypeptide length and sequence on VLP formation and morphology, in an insect cell expression system. Fused sequences included a modified reverse transcriptase-Tat-Nef fusion polypeptide (RTTN, 778 aa), and truncated versions of RTTN ranging from 113 aa to 450 aa. Baculovirus-expressed chimaeric proteins were examined by western blot and electron microscopy. All chimaeras formed VLPs which could be purified by sucrose gradient centrifugation. VLP diameter increased with protein MW, from ∼100 nm for Pr55Gag to ∼250 nm for GagRTTN. The presence or absence of the Gag p6 region did not obviously affect VLP formation or appearance. GagRT chimaeric particles were successfully used in mice to boost T-cell responses to Gag and RT that were elicited by a DNA vaccine encoding a GagRTTN polypeptide, indicating the potential of such chimaeras to be used as candidate HIV vaccines. © 2008 Elsevier B.V. All rights reserved.

A prime-boost immunisation regimen using recombinant BCG and Pr55 gag virus-like particle vaccines based on HIV type 1 subtype C successfully elicits Gag-specific responses in baboons

Mycobacterium bovis BCG is considered an attractive live bacterial vaccine vector. In this study, we investigated the immune response of baboons to a primary vaccination with recombinant BCG (rBCG) constructs expressing the gag gene from a South African HIV-1 subtype C isolate, and a boost with HIV-1 subtype C Pr55 gag virus-like particles (Gag VLPs). Using an interferon enzyme-linked immunospot assay, we show that although these rBCG induced only a weak or an undetectable HIV-1 Gag-specific response on their own, they efficiently primed for a Gag VLP boost, which strengthened and broadened the immune responses. These responses were predominantly CD8+ T cell-mediated and recognised similar epitopes as those targeted by humans with early HIV-1 subtype C infection. In addition, a Gag-specific humoral response was elicited. These data support the development of HIV-1 vaccines based on rBCG and Pr55 gag VLPs. © 2009 Elsevier Ltd. All rights reserved.

HIV-1 subtype C Pr55gag virus-like particle vaccine efficiently boosts baboons primed with a matched DNA vaccine

A DNA vaccine expressing human immunodeficiency virus type 1 (HIV-1) southern African subtype C Gag (pTHGag) and a recombinant baculovirus Pr55gag virus-like particle prepared using a subtype C Pr55gag protein (Gag VLP) was tested in a prime-boost inoculation regimen in Chacma baboons. The response of five baboons to Gag peptides in a gamma interferon (IFN-γ) enzyme-linked immunospot (ELISPOT) assay after three pTHGag immunizations ranged from 100 to 515 spot-forming units (s.f.u.) per 106 peripheral blood mononuclear cells (PBMCs), whilst the response of two baboons to the Gag VLP vaccine ranged from 415 to 465 s.f.u. per 106 PBMCs. An increase in the Gag-specific response to a range of 775-3583 s.f.u. per 106 PBMCs was achieved by boosting with Gag VLPs the five baboons that were primed with pTHGag. No improvement in Gag responses was achieved in this prime-boost inoculation regimen by increasing the number of pTHGag inoculations to six. IFN-γ responses were mapped to several peptides, some of which have been reported to be targeted by PBMCs from HIV-1 subtype C-infected individuals. Gag VLPs, given as a single-modality regimen, induced a predominantly CD8+ T-cell IFN-γ response and interleukin-2 was a major cytokine within a mix of predominantly Th1 cytokines produced by a DNA-VLP prime-boost modality. The prime-boost inoculation regimen induced high serum p24 antibody titres in all baboons, which were several fold above that induced by the individual vaccines. Overall, this study demonstrated that these DNA prime/VLP boost vaccine regimens are highly immunogenic in baboons, inducing high-magnitude and broad multifunctional responses, providing support for the development of these products for clinical trials. © 2008 SGM.

An investigation into the use of human papillomavirus type 16 virus-like particles as a delivery vector system for foreign proteins: N- and C-terminal fusion of GFP to the L1 and L2 capsid proteins

Development of vaccine strategies against human papillomavirus (HPV), which causes cervical cancer, is a priority. We investigated the use of virus-like particles (VLPs) of the most prevalent type, HPV-16, as carriers of foreign proteins. Green fluorescent protein (GFP) was fused to the N or C terminus of both L1 and L2, with L2 chimeras being co-expressed with native L1. Purified chimaeric VLPs were comparable in size (∼55 nm) to native HPV VLPs. Conformation-specific monoclonal antibodies (Mabs) bound to the VLPs, thereby indicating that they possibly retain their antigenicity. In addition, all of the VLPs encapsidated DNA in the range of 6-8 kb. © 2007 Springer-Verlag.

HIV-1 sub-type C chimaeric VLPs boost cellular immune responses in mice

Several approaches have been explored to eradicate HIV; however, a multigene vaccine appears to be the best option, given their proven potential to elicit broad, effective responses in animal models. The Pr55 Gagprotein is an excellent vaccine candidate in its own right, given that it can assemble into large, enveloped, virus-like particles (VLPs) which are highly immunogenic, and can moreover be used as a scaffold for the presentation of other large non-structural HIV antigens. In this study, we evaluated the potential of two novel chimaeric HIV-1 Pr55 Gag-based VLP constructs - C-terminal fusions with reverse transcriptase and a Tat::Nef fusion protein, designated GagRT and GagTN respectively - to enhance a cellular response in mice when used as boost components in two types of heterologous prime-boost vaccine strategies. A vaccine regimen consisting of a DNA prime and chimaeric HIV-1 VLP boosts in mice induced strong, broad cellular immune responses at an optimum dose of 100 ng VLPs. The enhanced cellular responses induced by the DNA prime-VLP boost were two- to three-fold greater than two DNA vaccinations. Moreover, a mixture of GagRT and GagTN VLPs also boosted antigen-specific CD8+ and CD4+ T-cell responses, while VLP vaccinations only induced predominantly robust Gag CD4+ T-cell responses. The results demonstrate the promising potential of these chimaeric VLPs as vaccine candidates against HIV-1. © 2010 Pillay et al; licensee BioMed Central Ltd.

DRD2/ANKK1 Taq1A (rs 1800497 C>T) genotypes are associated with susceptibility to second generation antipsychotic-induced akathisia

Rationale Although the advent of atypical, second-generation antipsychotics (SGAs) has resulted in reduced likelihood of akathisia, this adverse effect remains a problem. Extrapyramidal adverse effects are associated with increased drug occupancy of dopamine 2 receptors (DRD2). The A1 allele of the DRD2/ANKK1,rs1800497, is associated with decreased striatal DRD2 density. Objectives The aim of this study was to identify whether the A1(T) allele of the DRD2/ANKK1 was associated with akathisia (measured with the Barnes Akathisia Rating Scale) in a clinical sample of 234 patients treated with antipsychotics. Results Definite akathisia (a score≥ 2 for the global clinical assessment of akathisia) was significantly less common in subjects prescribed SGAs (16.8 %) than those prescribed FGAs (47.6%), p<0.0001. Overall, 24.1% of A1+ (A1A2/A1A1) patients treated with SGAs had akathisia compared to 10.8% of A1- (A2A2) patients. A1+ (A1A2/A1A1) patients administered SGAs also had higher global clinical assessment of akathisia scores than A1- subjects (p=0.01). SGAs maintained their advantage over FGAs regarding akathisia even in A1+ patients treated with SGAs. Conclusions These results strongly suggest that A1+ variants of the DRD2/ANKK1 Taq1A allele confer risk for akathisia in patients treated with SGAs and may explain inconsistencies across prior studies comparing FGAs and SGAs.

Average structure of an An (sub 48) plagioclase from the Hogarth Ranges

The average structure (CI) of a volcanic plagioclase megacryst with composition Ano, from the Hogarth Ranges, Australia, has been determined using three-dimensional, singlecrystal neutron and X-ray diffraction data. Least squaresr efinements, incorporating anisotropic thermal motion of all atoms and an extinction correction, resulted in weighted R factors (based on intensities) of 0.076 and 0.056, respectively, for the neutron and X-ray data. Very weak e reflections could be detected in long-exposure X-ray and electron diffraction photographs of this crystal, but the refined average structure is believed to be unaffected by the presence of such a weak superstructure. The ratio of the scattering power of Na to that of Ca is different for X ray and neutron radiation, and this radiation-dependence of scattering power has been used to determine the distribution of Na and Ca over a split-atom M site (two sites designated M' and M") in this Ano, plagioclase. Relative peak-height ratios M'/M", revealed in difference Fourier sections calculated from neutron and X-ray data, formed the basis for the cation-distribution analysis. As neutron and X-ray data sets were directly compared in this analysis, it was important that systematic bias between refined neutron and X-ray positional parameters could be demonstrated to be absent. In summary, with an M-site model constrained only by the electron-microprobedetermined bulk composition of the crystal, the following values were obtained for the M-site occupanciesN: ar, : 0.29(7),N ar. : 0.23(7),C ar, : 0.15(4),a nd Car" : 0.33(4). These results indicate that restrictive assumptions about M sites, on which previous plagioclase refinements have been based, are not applicable to this Ano, and possibly not to the entire compositional range. T-site ordering determined by (T-O) bond-length variation-t,o : 0.51(l), trm = t2o = t2m = 0.32(l)-is weak, as might be expectedf rom the volcanic origin of this megacryst.

Fresh water and acid sensitivity of authigenic clays in sandstone reservoirs

Authigenic illite-smectite and chlorite in reservoir sandstones from several Pacific rim sedimentary basins in Australia and New Zealand have been examined using an Electroscan Environmental Scanning Electron Microscope (ESEM) before, during, and after treatment with fresh water and HCl, respectively. These dynamic experiments are possible in the ESEM because, unlike conventional SEMs that require a high vacuum in the sample chamber (10-6 torr), the ESEM will operate at high pressures up to 20 torr. This means that materials and processes can be examined at high magnifications in their natural states, wet or dry, and over a range of temperatures (-20 to 1000 degrees C) and pressures. Sandstones containing the illite-smectite (60-70% illite interlayers) were flushed with fresh water for periods of up to 12 hours. Close examination of the same illite-smectite lines or filled pores, both before and after freshwater treatments, showed that the morphology of the illite-smectite was not changed by prolonged freshwater treatment. Chlorite-bearing sandstones (Fe-rich chlorite) were reacted with 1M to 10M HCl at temperatures of up to 80 degrees C and for periods of up to 48 hours. Before treatment the chlorites showed typically platy morphologies. After HCl treatment the chlorite grains were coated with an amorphous gel composed of Ca, Cl, and possibly amorphous Si, as determined by EDS analyses on the freshly treated rock surface. Brief washing in water removed this surface coating and revealed apparently unchanged chlorite showing no signs of dissolution or acid attack. However, although the chlorite showed no morphological changes, elemental analysis only detected silicon and oxygen.

Effect of bone morphogenetic protein-4 (BMP-4) on the expression of Sox2, Oct-4 and c-Myc in human periodontal ligament cells during long-term culture

Recent studies demonstrated endogenous expression level of Sox2, Oct-4 and c-Myc is correlated with the pluripotency and successful induction of induced pluripotent stem cells (iPSCs). Periondontal ligament cells (PDLCs)have multi-lineage diferentiation capability and ability to maintain undifferentiated stage, which makes PDLCs a suitable cell source for tissue repair and regeneration. To elucidate the effect of in vitro culture condition on the stemness potential of PDLCs, we explored the cell growth, proliferation, cell cycle, and the expression of Sox2, Oct-4 and c-Myc in PDLCs from passage 1 to 7 with or without the addition of recombinant human BMP4(rhBMP4). Our results revealed that BMP-4 promoted cell growth and proliferation, arrested PDLCs in S phase of cell cycle and upregulated PI value. It was revealed that without the addition of rhBMP4, the expression of Sox2, Oct-4 and c-Myc in PDLCs only maintained nucleus location until passage 3, then lost nucleus location subsequently. The mRNA expression in PDLCs further confirmed that the level of Sox2 and Oct-4 peaked at passage 3, then decreased afterwards, whereas c-Myc maintained consistently upregulation along passages. after the treatment with rhBMP4, the expression of Sox2, Oct-4 and c-Myc in PDLCs maintained nucleus location even at passage 7 and the mRNA expression of Sox2 and Oct-4 significantly upregulated at passage 5 and 7. These results demonstrated that addition of rhBMP-4 in the culture media could improve the current culture condition for PDLCs to maintain in an undifferentiated stage.

RcppArmadillo : accelerating R with high-performance C++ linear algebra

The R statistical environment and language has demonstrated particular strengths for interactive development of statistical algorithms, as well as data modelling and visualisation. Its current implementation has an interpreter at its core which may result in a performance penalty in comparison to directly executing user algorithms in the native machine code of the host CPU. In contrast, the C++ language has no built-in visualisation capabilities, handling of linear algebra or even basic statistical algorithms; however, user programs are converted to high-performance machine code, ahead of execution. A new method avoids possible speed penalties in R by using the Rcpp extension package in conjunction with the Armadillo C++ matrix library. In addition to the inherent performance advantages of compiled code, Armadillo provides an easy-to-use template-based meta-programming framework, allowing the automatic pooling of several linear algebra operations into one, which in turn can lead to further speedups. With the aid of Rcpp and Armadillo, conversion of linear algebra centered algorithms from R to C++ becomes straightforward. The algorithms retains the overall structure as well as readability, all while maintaining a bidirectional link with the host R environment. Empirical timing comparisons of R and C++ implementations of a Kalman filtering algorithm indicate a speedup of several orders of magnitude.